Biomedical subjects

S Higashide

Publications and source records attributed to S Higashide.

At least 19 recordsLinked to original sources

PubMed2001

Morphologic changes in the aorta during elastase infusion in the rat aneurysm model.

BACKGROUND: The morphologic changes in the aorta during elastase infusion, which have not previously been investigated, were examined in the rat abdominal aortic aneurysm model. MATERIALS AND METHODS: A total of 80 Wistar rats were divided into five groups. A 1.0-cm segment of infra-renal abdominal aorta was infused with 25 U of elastase in 1 mL saline for 10 (n = 14), 20 (n = 14), 30 (n = 14), 60 (n = 19), or 120 min (n = 19). In the 120-min group, transparency and aortic diameter were recorded every 10 min. In each group, 7 rats were killed immediately after infusion. The aortas were excised for histologic examination. The aortic diameters were measured 7 days after infusion in the remaining rats. RESULTS: The infused aorta became transparent within 50 min of elastase infusion. The aortic diameter increased rapidly for the first 30 min of infusion. Histologically, the elastic tissue was completely absent after 60 min of infusion. The aortic diameters in the 60- and 120-min groups were not significantly different 7 days after infusion. CONCLUSIONS: Morphologic changes in the infused aorta are complete after 60 min of elastase infusion. It may be possible to shorten the elastase infusion time from 120 to 60 min in this model.

Animals↗

PubMed2000

Factors influencing mortality in the rat elastase-induced-aneurysm model.

BACKGROUND: Intraarterial infusion of elastase has been used to create an experimental model of aortic aneurysm in rats. Unfortunately, the utility of this model is limited by a high mortality rate among experimental animals. This study examined the factors influencing mortality to help refine this model. MATERIALS AND METHODS: A total of 126 Wistar rats were divided into six groups. A 1.0-cm segment of infra-renal abdominal aorta was clamped (n = 21), clamped and cannulated via the femoral artery (n = 21), infused with saline (n = 21), or infused with solution containing 25 U of elastase from three different lots (each group, n = 21). Clamping or infusion was performed for 30 (n = 7), 60 (n = 7), and 120 min (n = 7). The mortality rates were calculated at 7 days. RESULTS: There were no deaths in the clamp group, but 29% of the rats that underwent cannulation with clamping or saline infusion for 2 h died. The mortality rate for a 30-min elastase infusion ranged from 0 to 71%. Mortality for a 60-min infusion ranged from 14 to 100%. Mortality for a 2-h infusion ranged from 43 to 100%. The mortality rate was dependent on the treatment time and the elastase lot number. CONCLUSIONS: Aortic cannulation, elastase infusion, and prolonged infusion times all increase the mortality rate in the elastase-induced rat aortic aneurysm model. Mortality is also dependent on the elastase lot number.

Animals↗

PubMed2000

The effect of immunosuppression on aortic dilatation in a rat aneurysm model.

This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model.

Animals↗

PubMed2000

The time course of elastin fiber degeneration in a rat aneurysm model.

Previous findings vary regarding the timing and cause of elastin fiber degeneration in the elastase-induced rat abdominal aortic aneurysm model. We examined the timing and cause of elastin fiber degeneration after elastase infusion using two different elastase infusion times. Twenty-four Sprague-Dawley rats were divided into two groups. The infrarenal abdominal aorta was infused with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n = 12, 30-min infusion group). In each group, three rats were killed immediately and 1, 3, and 7 days after infusion, and then the aortas were excised for a histologic examination. Elastin fibers did not stain, even immediately after elastase infusion, in the 30-min infusion group. The degeneration of elastin fibers did not progress in the 15-min infusion group during the period of observation. Inflammatory cells infiltrated mainly to the adventitia near regions where the degeneration of elastin fibers spread totally through the aortic media. Elastin fibers degenerate immediately after elastase infusion and thus seem to degenerate not due to endogenous proteinases that are produced by the infiltrating cells, but due to the exogenously infused elastase itself. Inflammatory cell infiltration was thus found to be a result of the degeneration of elastin fibers in this model.

Animals↗

PubMed1999

Shortened elastase infusion time in the elastase-induced rat aneurysm model.

OBJECTIVE: This study was performed to determine whether it would be possible to shorten the elastase infusion time in the elastase-induced rat aneurysm model. METHODS: The abdominal aortas of 76 male Sprague-Dawley rats were dissected and infused for 10, 20, 30, 60, or 120 min with a solution containing 14 U of elastase or for 30 min with saline solution (control). After infusion, the rats were evaluated every day for calculation of the mortality rate. On day 7, the surviving rats underwent laparotomy. The diameter of the aorta was measured, and the aortic tissue was excised for histologic examination. RESULTS: There were no deaths among the rats infused for 10, 20, or 30 min. The mortality rate was 64% in the 60-min and 90% in 120-min groups. There were no significant differences in the diameters of the 30-min saline-infused aortas and the 10- or 20-min elastase-infused aortas. The diameter of the 30-min elastase-infused aortas (6.2 +/- 2.1 mm) was significantly larger (P < 0.01) than the diameters of the 10- and 20-min elastase-infused aortas. There were no significant differences between the 30-min and the 60- and 120-min elastase-infused aortas. Microscopically, there was total or subtotal loss of elastic tissue and marked inflammatory cell infiltration of the aortic wall in the 30-, 60-, and 120-min elastase-infused aortas. CONCLUSIONS: It is possible to shorten the elastase infusion time from 120 to 30 min in the elastase-induced rat aneurysm model. This shortening of infusion time reduces the experimental time and mortality rate.

Animals↗

PubMed1997

Inhibition of neurotensin-induced pancreatic carcinoma growth by a nonpeptide neurotensin receptor antagonist, SR48692.

BACKGROUND: Recently, a nonpeptide neurotensin (NT) receptor antagonist, SR48692, was developed that selectively antagonizes the high affinity, biologically active NT binding site. The effect of SR48692 on NT-mediated growth of a human pancreatic carcinoma, MIA PaCa-2, was determined both in vitro and in vivo. METHODS: (125)I-NT binding and Northern blot analyses were performed for evaluation of the NT receptor in MIA PaCa-2 cells. Intracellular calcium ([Ca2+]i) mobilization and inositol phosphate (IP3) levels were measured. Cell growth studies were performed by counting cell numbers. Athymic nude mice were inoculated with MIA PaCa-2 cells and randomized into four groups to receive either vehicle (NT or SR48692) or NT + SR48692. RESULTS: MIA PaCa-2 cells possess both a high affinity, SR48692-sensitive and a levocabastine-insensitive NT binding site; Northern blot analysis demonstrated expression of the NT receptor. SR48692 inhibited [Ca2+]i mobilization, IP3 turnover, and MIA PaCa-2 cell growth induced by NT in a dose-dependent fashion. In in vivo experiments, NT significantly increased the size, weight, and DNA and protein content of xenografted MIA PaCa-2 tumors; SR48692 inhibited the effect of NT. CONCLUSIONS: The novel NT receptor antagonist SR48692 will be a valuable agent to delineate further the cellular mechanisms responsible for peptide-mediated growth of normal and neoplastic gut tissues.

Animals↗

PubMed1997

Caloric restriction causes secretagogue specific changes of gastric acid secretion in rats.

The purpose of this study was to examine the effects of short-term caloric restriction (CR) for 4, 8 and 16 weeks on gastric acid secretion in rats. CR rats fed 60% of normal food intake for 4, 8 or 16 weeks and then prepared with gastric fistulas. Histamine- and carbachol-stimulated gastric acid secretion were significantly (P < 0.05) decreased after more than 4 weeks and 8 weeks of caloric restriction, respectively. In contrast, gastrin-stimulated acid secretion was unaffected by CR. The 1-h-integrated acid output to a submaximal dose of gastrin (40 micrograms.kg-1) was significantly higher than that of histamine (5 mg.kg-1) after 8 weeks of CR (63 +/- 13 and 27 +/- 4 microEq.h-1, respectively). Gastrin treatment (5 micrograms.kg-1.h-1) of CR rats restored the gastric acid responses to both histamine and carbachol. These results suggest that CR can selectively decrease the gastric acid responses to both histamine and carbachol by depletion of the endogenous tissue stores of gastrin. More importantly, these results indicate that under an in vivo gastrin-diminished condition, histamine is not the final secretagogue for gastric acid secretion.

Animals↗

PubMed1997

Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin.

BACKGROUND & AIMS: Gastrin (G-17) stimulates the growth of certain gastric and colon cancers mostly through gastrin/cholecystokinin (CCK)-B receptors. Glycine-extended gastrin (Gly-G) stimulates growth of a rat pancreatic acinar cell line; however, the effect of Gly-G on human gastric cancers is not known. The purpose of this study was to characterize the trophic effect of G-17 and Gly-G on two human gastric cancer cell lines, AGS and SIIA. METHODS: Binding analyses were performed, and cell growth was assessed by counting cells over a time course. RESULTS: G-17 stimulated growth of both AGS and SIIA cells. In AGS cells, gastrin/CCK-B receptor antagonists inhibited the effect of G-17 and competitively antagonized 125I-G-17 binding, whereas the CCK-preferring (CCK-A) receptor antagonists had no effect. In contrast, CCK-A receptor antagonists inhibited the stimulatory effect of G-17 in SIIA cells, whereas CCK-B receptor antagonists had no effect. Gly-G stimulated the growth of AGS and SIIA cells; neither the CCK-B nor the CCK-A receptor antagonists blocked this effect. CONCLUSIONS: G-17 stimulates proliferation of AGS cells through the CCK-B receptor; however, G-17-mediated growth of SIIA acts through a CCK-A-like receptor. Furthermore, Gly-G stimulates growth of human gastric cancer cell lines, possibly through a receptor other than the CCK-B or CCK-A receptor.

Cell Division↗

PubMed1996

Glycine-extended gastrin potentiates gastrin-stimulated gastric acid secretion in rats.

The purpose of this study was to examine whether an intermediate form of amidated gastrin, glycine-extended gastrin (Gly-G), can stimulate gastric acid secretion in conscious rats prepared with gastric fistulas. Intravenous administration of Gly-G (20 nmol.kg-1.h-1) alone for 2 h did not stimulate gastric acid secretion; however, administration of Gly-G (20 nmol.kg-1.h-1) in combination with a bolus administration of gastrin (9.5 nmol/kg) potentiated acid secretion significantly. Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (2 nmol.kg-1.h-1) was 109.1 +/- 21.6 and 170.1 +/- 27.7 mueq.kg-1.h-1, respectively (P < 0.05). Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (20 nmol.kg-1.h-1) was 84.8 +/- 17.5 and 164.1 +/- 29.3 mueq.kg-1.h-1, respectively (P < 0.05). Intravenous administration of Gly-G (20 nmol.kg-1.h-1) failed to increase histamine (1 mg/kg)-stimulated acid output. These results demonstrate that Gly-G can selectively potentiate the stimulatory effect of gastrin on acid secretion in rats and that the unprocessed form of gastrin, Gly-G, can exert a biological effect in the stomach.

Animals↗

PubMed1995

Effects of cyclosporine and tacrolimus (FK 506) on acute pancreatitis in mice.

OBJECTIVE: To use mice to examine the effects of cyclosporine and tacrolimus (FK 506) on two forms of acute pancreatitis often seen after clinical organ transplantation. METHODS AND DESIGN: In the first experiment, male CD-1 mice received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline solution (control) subcutaneously once a day for 10 days. On the 11th day, acute edematous pancreatitis was induced by ceruletide (cerulein). In the second experiment, female ICR mice were fed with a choline-deficient, ethionine-supplemented (CDE) diet for 72 hours to induce necrotizing pancreatitis. After 30 hours on the CDE diet, the mice received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline solution (control) subcutaneously twice daily for 3 days. RESULTS: The pancreatic dry-to-wet weight ratios after ceruletide injections significantly decreased in mice treated with cyclosporine but did not with tacrolimus. Cyclosporine also significantly increased serum amylase levels, but tacrolimus did not. Cyclosporine or tacrolimus alone did not produce pancreatitis. In the CDE diet groups there was a significant difference in survival among the cyclosporine-treated, the tacrolimus-treated, and the control groups. CONCLUSIONS: Cyclosporine or tacrolimus given alone does not induce acute pancreatitis. In contrast, cyclosporine can adversely affect the course of acute edematous pancreatitis, and both immunosuppressants may worsen the survival of mice with acute hemorrhagic necrotizing pancreatitis. This study also demonstrated that the deteriorating effect of tacrolimus is less potent than that of cyclosporine.

Acute Disease↗

PubMed1995

Protective effects of endothelin-1 on acute pancreatitis in rats.

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.

Acute Disease↗

PubMed1995

Bombesin stimulates mucosal growth in jejunal and ileal Thiry-Vella fistulas.

OBJECTIVE: The authors determined whether the trophic effects of bombesin (BBS) on the small bowel mucosa are mediated by either nonluminal factors or endogenous luminal secretion. SUMMARY BACKGROUND DATA: The gut hormone bombesin stimulates growth of small bowel mucosa. The mechanisms responsible for this trophic effect are not known. METHODS: Rats underwent construction of a Thiry-Vella fistula (TVF) of either the jejunum or ileum. On postoperative day 10, the two groups were subdivided to receive either saline (control) or bombesin (10 micrograms/kg, subcutaneously, three times a day). After 14 days, rats were killed and the TVF was removed. The mucosa was scraped and weighed, and DNA and protein content was determined. RESULTS: Bombesin significantly increased mucosal weight and DNA and protein content of both the jejunal and ileal TVF compared with the control rats. CONCLUSIONS: Bombesin-mediated stimulation of small bowel mucosal growth is mediated by factors that are independent of luminal contents and pancreaticobiliary secretion. Bombesin may prove to be an important enterotrophic factor for gut mucosal proliferation.

Animals↗

PubMed1995

Effect of a new bombesin receptor antagonist, (E)-alkene bombesin isostere, on amylase release from rat pancreatic acini.

The short-chain pseudopeptide, [D-Phe6, Leu13 psi (CH2NH)Leu14]bombesin(6-14) (RDI), is reported to be a potent antagonist of bombesin, and development of this type of compound has greatly contributed to the investigation of biological actions of bombesin and its related peptides. We recently synthesized (E)-alkene bombesin isostere by replacing the peptide bond with an (E)-double bond: [D-Phe6, Leu13 psi [(E)CH = CH]Leu14] bombesin(6-14) (EABI). The present study examined the effect of EABI on amylase release from rat pancreatic acini. EABI showed no agonistic activity at concentrations up to 1 microM, and RBI showed slight agonistic activity at concentrations > 10 nM. EABI caused a dose-dependent inhibition of amylase release stimulated by 0.1 nM bombesin, with an IC50 of 6.7 +/- 1.7 nM, and induced almost-complete inhibition at 0.3 microM. RDI caused a dose-dependent inhibition of amylase release, with an IC50 of 68.7 +/- 16 nM. EABI caused a parallel and rightward shift of the entire dose-response curve of bombesin-stimulated amylase release, and the degree of the shift was dependent on the concentrations of EABI. EABI (100 nM) and RDI (100 nM) inhibited amylase releases stimulated by gastrin-releasing peptide (1 nM) and neuromedin-C (1 nM). In contrast, amylase release stimulated by cholecystokinin octapeptide (0.1 nM), carbachol (10 microM), vasoactive intestinal peptide (1 nM), and gastrin-17 (10 nM) was not inhibited by EABI and RDI. The results indicate that EABI is a potent and specific bombesin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.

Animals↗

PubMed1992

Expression of epidermal growth factor receptor after partial pancreatectomy in adult rats: an immunohistochemical study.

The expression and localization of epidermal growth factor (EGF) were investigated immunohistochemically using an anti-EGF receptor antibody in the pancreas of partial pancreatectomized and sham-operated adult rats. In the sham-operated pancreas, immunoreactive products against EGF receptor were only slightly positive in the pancreatic acinar cells. In the partial pancreatectomized pancreas on the fifth day after operation, EGF receptor immunoreactivity was intensely positive in the acinar cells, in some cells lining the intercalated ducts and some basal cells of the acinus, but it was not detected in the pancreas when exogenous EGF was given to the rat after partial pancreatectomy for three days. The present results suggest that EGF receptor is expressed in the regenerating pancreatic tissue, and EGF could be involved in the mechanism of pancreatic regeneration in rats.

Animals↗

PubMed1992

Immunohistochemical study on epidermal growth factor (EGF) receptor during carcinogenesis in the rat liver.

The expression and localization of epidermal growth factor (EGF) receptor were investigated immunohistochemically using anti-EGF receptor antibody in the normal rat liver and 3'-methyl-4-dimethylaminoazobenzen (3'-Me-DAB) induced tumors in rats. In 8 weeks after 3'-Me-DAB treatment, multiple nodules of cholangiocarcinoma were found in the rat liver, and atypical nodules of hepatocytes were also found 14 weeks later. Immunoreactive products against EGF receptor were only slightly positive in the normal liver, the nodule of cholangiocarcinoma, and atypical nodule of hepatocytes. It was noted that EGF receptor immunoreactivity was more intense in non-cancerous tissue adjacent to tumorous nodules than in the cancerous tissue. The present finding suggests that the expression of EGF receptor may be associated with regenerating as well as carcinogenetic processes in the rat liver.

Adenoma, Bile Duct↗

PubMed1992

Metabolic bone disease following gastrectomy: assessment by dual energy X-ray absorptiometry.

Although disorders in bone metabolism have long been recognized as typical sequelae of gastrectomy, there has until now been no reliable method of providing precise assessment of bone mass, resulting in a variation of reported incidence. In this study, metabolic bone disease was evaluated in a well characterized population: 34 men 2-5 years after gastrectomy; 11 men 6-10 years after gastrectomy; eight men 2-5 years after colonic resection; and 115 healthy men. The age range was 50-69 years. An innovative reliable method of dual energy X-ray absorptiometry was used which allows quantitative assessment of bone mineral content. Measurement of lumbar spine bone mineral density revealed that the mean(s.e.m.) bone mineral density in patients who had had a gastrectomy (2-5 years 0.84(0.03) g/cm2, 6-10 years 0.85(0.05) g/cm2) was significantly lower than that of patients who had undergone colonic resection (0.96(0.04) g/cm2) or healthy men (0.96(0.03) g/cm2). This study demonstrates that a high incidence of bone atrophy is induced at the relatively early period of 2-5 years after gastrectomy.

Absorptiometry, Photon↗

PubMed1992

Effects of endothelin on microcirculation of the pancreas.

Endothelin, a newly described endothelial-derived peptide, has potent vasoconstrictive properties and has been speculated to play a physiological role in the regulation of blood flow in some organs. The present study was designed to evaluate the effects of endothelin-1, endothelin-2 and endothelin-3 on the pancreatic microcirculation. Pancreatic tissue blood flow was measured by a laser Doppler flow meter in anesthetized dogs and endothelin-1, endothelin-2 or endothelin-3 was injected intravenously in graduated doses. Endothelins induced dose-dependent decreases in pancreatic tissue blood flow. Endothelin-1, endothelin-2 and endothelin-3 at a dose of 100 pmol/kg reduced pancreatic blood flow by 45.4%, 19.6% and 51.9%, respectively, whereas systemic arterial blood pressure was not significantly affected. When endothelin-3 was administered at a dose of 1000 pmol/kg, pancreatic blood flow was decreased by 73.5% with a concomitant increase of systemic arterial blood pressure by 17.6%. Endothelins potently decreased pancreatic tissue blood flow, suggesting a possible role of these agents in regulating the pancreatic microcirculation.

Analysis of Variance↗